Popular Articles

Novel Genome Editing With Crispr-Cas9, Lara Janiszewski

Undergraduate Honors Theses

There are 9 Let7 family members present in keratinocytes, all acting as translational suppressors of the same target mRNAs. This redundancy implies that Let7 is crucial to cellular functioning, and it has indeed been found to act as a tumor suppressor, down regulating functions such as proliferation, cell motility, and de-differentiation. I hypothesized that increasing loss of Let7 loci would lead to progressively more tumor-like phenotypes in the cells. Phenotypic analysis of these cells has not yet been possible, but initial Let7 knockouts were successful.

The amyloid precursor protein is found on chromosome 21 and is strongly upregulated in individuals ...

Faculty Publications, Department of Child, Youth, and Family Studies

For decades, researchers have investigated how events in the prenatal period impact women and their infants. These studies, particularly by researchers in the medical, neuroscience, and behavioral science fields, led to discoveries of important information regarding the prenatal events that were strongly associated with mortality (or death) and morbidity (or incidences of injury, pathology and abnormalities/anomalies, and neurobehavioral sequelae) in the neonatal and infancy periods. Among the many common findings from early research studies, two are particularly noteworthy. First, maternal and fetal risk conditions arising in the prenatal period do not do so in isolation. Sameroff and Chandler characterized ...

Chemical and Biological Engineering Publications

The pathogenesis of cancer is often driven by local invasion and metastasis. Recently, mechanical properties of the tumor microenvironment have been identified as potent regulators of invasion and metastasis, while matrix metalloproteinases (MMPs) are classically known as significant enhancers of cancer cell migration and invasion. Here we have been able to sensitively measure MMP activity changes in response to specific extracellular matrix (ECM) environments and cell contractility states. A pancreatic cancer cell line, Panc-1 cells, up-regulate MMP activities between 3- and 10- fold with increased cell contractility. Conversely, they down-regulate MMP activities when contractility is blocked to levels seen with ...

Publicly Accessible Penn Dissertations

ABSTRACT

CELLULAR MECHANISMS OF MAMMALIAN LIVER REGENERATION

Kilangsungla Yanger

Ben Z. Stanger

The liver is an essential organ that aids in metabolic processes, protein synthesis and detoxification of harmful substances. As the centre for detoxification, the liver is able to compensate for this routine damage with its robust regenerative ability. All vertebrate livers, for example, can make up for tissue mass loss (via surgical excision of a portion of the liver) by replication of their differentiated cells within the remnant lobes. These differentiated cells include parenchymal cells such as the hepatocytes and biliary epithelial cells (BECs) and also non-parenchymal cells ...

Once Upon A Microscopic Slide: The Story Of Histology, Inaya Hussein, Mohamad Raad, Rawan Safa, Rosalyn A. Jurjus, Abdo Jurjus

Anatomy and Regenerative Biology Faculty Publications

For centuries, histology has maintained its remarkable place in the medical curriculum. However, its teaching has been influenced by the new technological advancement that has reshaped medicine teaching into a more modern student-friendly form. Since its inception in the 18th century, the discipline of histology has progressed hand in hand with the advancements in microscopy and microscopic technologies, including immunohistochemistry. In the traditional curriculum of USA medical schools, especially after the first Flexner’s report of 1910, histology was considered as very essential topic for a physician studying the “Art and Science” of medicine. In this era, the teaching relied ...

Graduate Theses and Dissertations

Taxa with large geographic ranges experience considerable variation in climate. To the extent these organisms have environmentally sensitive traits, they provide an excellent opportunity to evaluate how different populations have responded to dissimilar local climates. These eco-evolutionary processes are of particular interest in organisms with traits that are intrinsically connected to temperature, such as embryonic development in oviparous taxa. Maternal effects, particularly oviposition-site choice, greatly affect offspring phenotypes and survival, and thus have the potential to mitigate the effects of divergent climatic conditions across a species range.

In our first study, we delineated natural nesting areas in each of six ...

Electronic Thesis and Dissertation Repository

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America. The highest risk factor for PDAC is recurrent pancreatitis. While the link between PDAC and pancreatitis is unknown, de-differentiation of acinar cells is common to both diseases. Our lab has shown that Activating Transcription Factor 3 (ATF3), a factor upregulated during pancreatic injury, contributes to the development of acinar-to-ductal cell metaplasia (ADM), a precursor phenotype of PDAC. The goal of this study was to identify how ATF3 contributes to ADM. I hypothesize that ATF3 regulates acinar gene expression promoting ADM. We observed decreased ADM development ...

Electronic Thesis and Dissertation Repository

Generally, all bilaterans examined have similar conservation of HOX protein structure, function, expression, and requirement. However, at the level of being the same, it is unknown whether the HOX protein, Antennapedia, is required for tarsus determination in Drosophilamelanogaster as in Tribolium casteneum, or whether the requirement of HOX proteins in determination of body parts diverges in insects. I proposed to use a heat shock-inducible nanobody (UAS- NSlmb-vhhGFP4 driven by hsp-GAL4) activated during the third larval stage in all cells to degrade thoracically expressed HOX proteins (Sex combs reduced, Antennapedia, and Ultrabithorax) tagged with green fluorescence protein (GFP) derivatives; GFP ...

Mechanisms Of Nitrogenous Waste Excretion During The Complex Life Cycle Of The Sea Lamprey (Petromyzon Marinus), James M. Neal Mr.

Theses and Dissertations (Comprehensive)

Sea lampreys (Petromyzon marinus) are a phylogenetically ancient jawless fish, with a multi-staged life cycle characterized by a prolonged suspension-feeding larval stage, which is followed by metamorphosis into parasitic lampreys that feed on the protein-rich blood of fishes. The switch from a nutrient poor to protein-rich diet in the sea lamprey is associated with an increased capacity to deaminate excess amino acids and to excrete ammonia and urea following metamorphosis. The focus of this thesis was to determine if changes in nitrogenous waste transporter protein abundance facilitate ammonia and urea excretion during different stages of the sea lamprey life cycle ...

Electronic Theses, Projects, and Dissertations

Though it is well known that tobacco related products can cause prenatal maldevelopment, very little is known on how tobacco products affect bone tissue as it develops in the embryo. Identifying which chemicals can induce the greatest harm to the prenatal skeletal system is an improbable task as there are over 7,000 chemicals in tobacco smoke alone. We hypothesized that the Toxicological Priority Index (ToxPI) program can be used to rank osteogenic cytotoxicity potential to aid in the assessment of what chemicals out of the thousands can cause osteogenic differentiation inhibition. ToxPI aggregates information from various assays and incorporates ...

MSU Graduate Theses

Fetal serotonin levels are involved in the development of the serotonergic system in an autoregulatory manner as well as the organization and connectivity of non-serotonergic neurons. Insufficient serotonin levels during development result in improper neuronal maturation and decreased synaptogenesis. Conversely, excess developmental serotonin levels can alter the progression of serotonergic neurons, ultimately resulting in a chronic decrease of serotonin in the developed brain via a negative feedback mechanism. There is a known correlation between autistic patients and chronically decreased brain serotonin concentrations; this is potentially implicated in the impaired development of the autistic brain. Incomplete or delayed development of motor ...

Posters-at-the-Capitol

Protein prenylation is a post-translational modification that involves the addition of lipid groups to the end of a target protein and is necessary for protein activity. Prenylation has important roles in the cell: targeting and localizing proteins to subcellular compartments and promoting protein-protein interactions. Recently, we have found Protein Prenyltransferase Alpha Subunit-like (PPAL), which shares structural similarities to known prenylation enzymes. However, the biochemical function of PPAL is still unknown. PPAL is present in a single copy in other plants examined to date but is present in two copies in moss. Knockouts in our lab of either PpPAL1 or PpPAL2 ...

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR ...

Open Access Articles

Regulation of chromatin structure is critical for cell type-specific gene expression. Many chromatin regulatory complexes exist in several different forms, due to alternative splicing and differential incorporation of accessory subunits. However, in vivo studies often utilize mutations that eliminate multiple forms of complexes, preventing assessment of the specific roles of each. Here we examined the developmental roles of the TIP55 isoform of the KAT5 histone acetyltransferase. In contrast to the pre-implantation lethal phenotype of mice lacking all four Kat5 transcripts, mice specifically deficient for Tip55 die around embryonic day 11.5 (E11.5). Prior to developmental arrest, defects in heart ...

LSAMP Poster Presentations

Starvation-resistant Drosophila melanogaster, common fruit flies, deriving from 121 generations of starvation selection, have resulted in genetically, behaviorally, and physiologically different individuals compared to non-resistant counterparts. Starvation-resistant Drosophila are more obese, containing twice as much lipids as control flies.This is a result of starvation-resistant fly larva feeding for 5 days and then entering the pupa stage while non-resistant flies only feed for 4 days.

In this experiment, we hope to answer the question of whether the starvation-resistant flies are genetically predisposed to be substantially more obese than wild populations or if it is a result of this alternate behavior ...

All Dissertations, Theses, and Capstone Projects

The maintenance of homeostatic functions is key to the survival and well-being of an organism. Regulation of homeostasis relies on varied inputs, both intrinsic and extrinsic, to potentiate a web of interconnected signaling relays. Insulin/IGF-1 signaling (IIS) is a well-known regulator of glucose and lipid metabolism, as well as having far reaching effects in other homeostatic mechanisms. On the other hand, bone morphogenetic protein (BMP), a member of the transforming growth factor beta signaling superfamily, is known for its role in differentiation and development, with only recent studies highlighting potential roles in metabolic homeostasis. Here we elucidate new functions ...

Open Access Articles

Zinc transporters facilitate metal mobilization and compartmentalization, playing a key role in cellular development. Little is known about the mechanisms and pathways of Zn movement between Zn transporters and metalloproteins during myoblast differentiation. We analyzed the differential expression of ZIP and ZnT transporters during C2C12 myoblast differentiation. Zn transporters account for a transient decrease of intracellular Zn upon myogenesis induction followed by a gradual increase of Zn in myotubes. Considering the subcellular localization and function of each of the Zn transporters, our findings indicate that a fine regulation is necessary to maintain correct metal concentrations in the cytosol and subcellular ...

Investigation Of Lin-28 Function In Somatic Gonadal Development And Fertility, And Characterization Of The Lin-28 Isoforms In C. Elegans Hermaphrodites, Sungwook Choi

GSBS Dissertations and Theses

lin-28 was first characterized as a developmental timing regulator in Caenorhabditis elegans. Loss of lin-28 function (lin-28(lf)) mutants skip the hypodermal cell fates specific to the 2nd larval stage. Here, we studied two aspects of lin-28 which had not yet been investigated.

First, we show that lin-28(lf) mutants exhibit reduced fertility associated with abnormal somatic gonadal morphology. In particular, the abnormal spermatheca-uterine valve morphology of lin-28(lf) hermaphrodites traps embryos in the spermatheca, which disrupts ovulation and causes embryonic lethality. The same genes downstream of lin-28 in the regulation of hypodermal developmental timing also act downstream of ...

Georgia Journal of Science

Sea urchin pigment cells are single cells of mesodermal origin embedded in the aboral ectoderm. Strongylocentrotus purpuratus polyketide synthase 1 (Sp-PKS1) is required for the biosynthesis of the echinochrome pigment. Evidence suggests that pigment cells are immune cells. In order to reconstruct the gene regulatory network of pigment cells a bottom-up approach combined with comparative genomics has been used in this study. We compared the cis-regulatory regions of five pigment cell genes, Sp-Pks1, flavin monooxygenase1, 2, and 3 (Sp-Fmo) and sulfotransferase (Sp-Sult), across three different species, Strongylocentrotus purpuratus, Mesocentrotus franciscanus, and Strongylocentrotus fragilis. The computational tool used was ...

Effect Of Arsenic Exposure On Early Eye Development In Zebrafish (Danio Rerio), Remy S. Babich

Electronic Theses and Dissertations

Arsenic is a metalloid that contaminates drinking water supplies worldwide. Due to concerns for human health, the World Health Organization (WHO) and the U.S. Environmental Protection Agency (EPA) have established a safe level in drinking water of ≤ 10 ppb. Arsenic has been shown to have carcinogenic effects in humans at high and low doses. Chronic exposure may result in dermal conditions such as hyperkeratosis and hyperpigmentation. Recently, arsenic exposure has also been linked to lower IQ values in children. The effect of arsenic on neurogenesis, specifically eye development, has not been widely explored. This study aimed to examine the ...

Growing Up In Tell El-Amarna: An Examination Of Growth And Non-Specific Stress Indicators In New Kingdom Children., Ashley Elizabeth Shidner

Theses and Dissertations

The health status of the subadult skeletal remains from the South Tombs Cemetery at Tell el-Amarna were assessed by examining fluctuations in childhood growth and rates of skeletal indicators of physiological stress within a biocultural framework. The long bone standardization method outlined by Goode et al. (1993) was used to compare the South Tombs cemetery’s cross-sectional growth data to subadult samples from other cemeteries during which major social, political, and economic changes were taking place. The comparative subadult samples included the HK43 cemetery from Hierakonpolis (Egypt), the African American Cemetery from Cedar Grove (Arkansas), and the St. Martin’s ...

Open Access Articles

Cancer cachexia (CC) is a multifactorial syndrome with an unknown etiology. The primary symptom is the progressive reduction of the body weight. Recently, down-regulation of adipogenic and lipogenic genes were demonstrated to be early affected during cachexia progression in adipose tissue (AT), resulting in AT remodeling. Thus, this study aimed to evaluate in a co-culture system the influence of the Lewis Lung Carcinoma (LLC) tumor cells (c/c-LLC) in an established pre-adipocyte cell line 3T3-L1 adipogenic capacity. c/c-LLC in the presence of 3T3-L1 caused a reduction in lipids accumulation, suggesting that secretory tumor cells products may affect adipogenesis. Interestingly ...

Pedro J. Llanos (www.AstronauticsLlanos.com)

Suborbital spaceflights, carrying scientific payloads, allow scientists not only to test the feasibility of their payloads, but they also provide the basis for refining scientific hypotheses to be later tested on the International Space Station (ISS). Therefore, it is essential to establish robust pre-flight procedures in order to take advantage of this unique research platform to facilitate payload delivery. In the present study, we assessed zebrafish larvae behavior as a precursor for the future suborbital spaceflight involving research on the musculoskeletal system. Zebrafish larvae were exposed to the same physiological stressors they would encounter during suborbital spaceflight: alterations in light ...

Open Access Articles

BACKGROUND: The ETS transcription factor ETV4 is involved in the main steps of organogenesis and is also a significant mediator of tumorigenesis and metastasis, such as in breast cancer. Indeed, ETV4 is overexpressed in breast tumors and is associated with distant metastasis and poor prognosis. However, the cellular and molecular events regulated by this factor are still misunderstood. In mammary epithelial cells, ETV4 controls the expression of many genes, MMP13 among them. The aim of this study was to understand the function of MMP13 during ETV4-driven tumorigenesis.

METHODS: Different constructs of the MMP13 gene promoter were used to study the ...

Open Access Articles

The linker histone H1 is critical to maintenance of higher-order chromatin structures and to gene expression regulation. However, H1 dynamics and its functions in embryonic development remain unresolved. Here, we profiled gene expression, nucleosome positions, and H1 locations in early Drosophila embryos. The results show that H1 binding is positively correlated with the stability of beads-on-a-string nucleosome organization likely through stabilizing nucleosome positioning and maintaining nucleosome spacing. Strikingly, nucleosomes with H1 placement deviating to the left or the right relative to the dyad shift to the left or the right, respectively, during early Drosophila embryonic development. H1 occupancy on genic ...

Life and Environmental Sciences Course-based Research Projects

In this project, we aimed to answer the question: Does cellular radiation affect offspring production and expression of the Rad51 gene in the organism Drosophila melanogaster? It was hypothesized that if Drosophila larvae were exposed to cellular radiation, the total offspring production would decrease, along with a corresponding increase in Rad51 expression. The Rad51 protein is crucial to the propagation of strand invasion and exchange steps in homologous recombination, resulting in the repair of double stranded DNA breaks. To test our hypothesis, we exposed the experimental group of Drosophila larvae to doses of cellular radiation emitted from an iPhone 6 ...

Life and Environmental Sciences Course-based Research Projects

Manganese is prevalent in Montana, and Manganese toxicity symptomatically resembles Parkinsons disease. The goal of this project was to determine whether exposure to high levels of Manganese affects the Dopamine synthesis pathway. For our experiment, we chose to measure the expression of the ple gene in Drosophila melanogaster that were exposed to Manganese during development. The ple gene codes for Tyrosine Hydroxylase, an enzyme that functions in the first rate-limiting step of Dopamine synthesis. We hypothesized that an abundance of Manganese would result in decreased expression of ple in larvae and observable motor function deficits among adult flies. To carry ...

Life and Environmental Sciences Course-based Research Projects

In this study, Tetrahymena thermophila cultures were exposed to an acute treatment of UV light and expression of the FBP1 gene was examined. The FBP1 gene encodes Fructose- 1,6-biphosphatase which plays an important role in the process of gluconeogenesis. It was hypothesized that exposure of Tetrahymena to UV light would cause an upregulation in DNA repair enzymes, thereby causing these cells to require higher levels of glucose. The higher demand for glucose would then result in the upregulation of gluconeogenesis and FBP1. Following acute exposure of Tetrahymena cultures to UV light, the expression of FBP1 was analyzed using reverse ...